The objective of this project is to identify a gene responsible for autosomal dominant congenital cataract. Because this identification has proven difficult in the human, the project will focus on a mouse model. Identification of the gene in the mouse would enable us to identify the homologous gene in the human. Our specific aims are: to perform linkage studies in order to identify the closest marker to the Hfi locus; to screen yeast artificial chromosome (YAC) libraries containing mouse genomic DNA; and finally to isolate and characterize a cDNA responsible for the Hfi mutation. To identify the closest marker, genomic DNA of backcross progeny will be screened with polymorphic markers. Having identified a close marker, a YAC library will be screened with that marker. The positive YAC clones will be mapped and further analyzed for the presence of candidate genes by exon trapping. Once identified, exon sequences will facilitate identification of the full length Hfi cDNA.